Epstein-Barr virus (EBV) is associated with both B cell cancers (Hodgkin lymphoma, Burkitt lymphoma) and epithelial cell cancers (nasopharyngeal carcinoma, gastric carcinoma). We previously reported that higher levels of antibody targeting EBV glycoprotein350 (gp350), an EBV vaccine candidate, were protective against nasopharyngeal carcinoma in genetically high-risk families from Taiwan. This year we attempted to extend this association to a general population cohort. We compared total and IgA-specific gp350 antibody levels in 35 incident cases of nasopharyngeal carcinoma and 81 disease-free controls from the Cancer Screening Program in Taiwan (23,943 individuals recruited from 1991-1992). Luciferase immunoprecipitation (LIPS) assays were used to quantify gp350 antibody levels. Total EBVgp350 antibody levels were not higher in individuals who remained disease-free compared to those who developed nasopharyngeal carcinoma (P=0.11). This lack of a protective EBV gp350 antibody association persisted for cases diagnosed >5 years (OR=1.05; P=0.91) and <5 years (OR=1.85; P=0.40) after blood draw. In addition, IgA-specific gp350 antibody levels were higher in cases compared to controls (OR=7.03; P=0.001). This increased risk was most pronounced for cases diagnosed <5 years after their blood draw (OR=11.7; P=0.004). Unlike our prior findings in those with a strong family history of NPC, total gp350 antibody levels were not protective against NPC development in this general population setting. We continue to follow and study a number of patients with EBV diseases, including those with chronic active EBV, EBV hydroa vacciniforme, and EBV lymphoproliferative diseases.